The proposed research will exploit the dopamine receptor binding ability of chlorpromazine and its congeners as kinetics probes in an exploration of the mechanisms of phenothiazine and neural transmitter binding by the dopamine receptor, thereby providing simultaneous information regarding the pharmacological mode of action of the drug, and kinetics characterization of the dopamine receptor. In this way, a potent drug will be used as a direct fluorescence probe of the membrane binding in much the same fashion that curare-like compounds and snake venom alpha-toxins have been exploited in the characterization of the acetylcholine receptor protein. Since such reactions occur swiftly, the techniques of computer-controlled stopped-flow fluorescence spectro-photometry will be employed to obtain kinetics data on the neurochemical millisecond time scale. Effects of calcium, dopamine and norepinephrine will be studied, and rat-brain synaptosomes and microsomes obtained from animals conditioned to long term exposure to chlorpromazine will also be investigated to establish whether such exposure leads to configurational modification of the receptor membrane protein. Kinetics studies of chlorpromazine metabolites will also be undertaken.